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|Ref Type||Journal Article|
|Authors||Turcotte S, Chan DA, Sutphin PD, Hay MP, Denny WA, Giaccia AJ|
|Title||A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.|
|Date||2008 Jul 8|
|Abstract Text||Renal cell carcinomas (RCCs) are refractory to standard therapies. The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in 75% of RCCs. By screening for small molecules selectively targeting VHL-deficient RCC cells, we identified STF-62247. STF-62247 induces cytotoxicity and reduces tumor growth of VHL-deficient RCC cells compared to genetically matched cells with wild-type VHL. STF-62247-stimulated toxicity occurs in a HIF-independent manner through autophagy. Reduction of protein levels of essential autophagy pathway components reduces sensitivity of VHL-deficient cells to STF-62247. Using a yeast deletion pool, we show that loss of proteins involved in Golgi trafficking increases killing by STF-62247. Thus, we have found a small molecule that selectively induces cell death in VHL-deficient cells, representing a paradigm shift for targeted therapy.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|VHL negative||renal cell carcinoma||sensitive||STF-62247||Preclinical||Actionable||In a preclinical study, STF-62247 induced selective cytotoxicity and inhibited tumor growth of renal cell carcinoma cells lacking VHL (PMID: 18769110, PMID: 18598947).||18769110 18598947|